Retrograde regulation of STIM1-Orai1 interaction and store-operated Ca2+ entry by calsequestrin.

ABSTRACT: Interaction between the endoplasmic reticulum (ER)-located stromal interaction molecue1 (STIM1) and the plasma membrane-located Ca(2+) channel subunit, Orai1, underlies store-operated Ca(2+) entry (SOCE). Calsequestrin1 (CSQ1), a sarcoplasmic reticulum Ca(2+) buffering protein, inhibits SOCE, but the mechanism of action is unknown. We identified an interaction between CSQ1 and STIM1 in HEK293 cells. An increase in monomeric CSQ1 induced by depleted Ca(2+) stores, or trifluoperazine (TFP), a blocker of CSQ folding and aggregation, enhanced the CSQ1-STIM1 interaction. In cells with Ca(2+) stores depleted, TFP further increased CSQ1 monomerization and CSQ1-STIM1 interaction, but reduced the association of STIM1 with Orai1 and SOCE. Over-expression of CSQ1 or a C-terminal (amino acid 388-396)

SUBMITTER: Wang L 

PROVIDER: S-EPMC4471903 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature